Synchronous Multiple Gastric Cancer Research Articles

Endoscopic Features of Synchronous Multiple Early Gastric Cancers: Findings from a Nationwide Cohort

Introduction: We investigated the factors associated with synchronous multiple early gastric cancers and determined their localization. Methods: We analyzed 8,191 patients who underwent endoscopic submucosal dissection for early gastric cancers at 33 hospitals in Japan from November 2013 to October 2016. Background factors were compared between single-lesion (n = 7,221) and synchronous multi-lesion cases (n = 970) using univariate and multivariate analyses. We extracted cases with two synchronous lesions (n = 832) and evaluated their localization. Results: Significant independent risk factors for synchronous multiple early gastric cancer were older age (≥75 years old) (odds ratio [OR] = 1.257), male sex (OR = 1.385), severe mucosal atrophy (OR = 1.400), tumor localization in the middle (OR = 1.362) or lower region (OR = 1.404), and submucosal invasion (OR = 1.528 [SM1], 1.488 [SM2]). Depressed macroscopic type (OR = 0.679) and pure undifferentiated histology OR = 0.334) were more common in single early gastric cancers. When one lesion was in the upper region, the other was more frequently located in the lesser curvature of the middle region. When one lesion was in the middle region, the other was more frequently located in the middle region or the lesser curvature of the lower region. When one lesion was in the lower region, the other was more frequently located in the lesser curvature of the middle region or the lower region. Conclusion: Factors associated with synchronous multiple early gastric cancer included older age, male sex, severe mucosal atrophy, tumor localization in the middle or lower region, and tumor submucosal invasion. Our findings provide useful information regarding specific areas that should be examined carefully when one lesion is detected.

Risk factors for remnant gastric cancer after distal gastrectomy for gastric cancer: a retrospective database review.

The number of patients with remnant gastric cancer (RGC) following gastrectomy for gastric cancer (GC) is increasing due to the increasing number of patients undergoing function-preserving gastrectomy and improved outcomes for patients with GC. A few studies involving a small number of cases reported male sex, old age, differentiated type, tumor depth and synchronous multiple GC were associated with RGC development. However, the risk factors for RGC development had not been fully understood. This study aimed to examine the clinicopathological features, followed up patients with GC after they underwent distal gastrectomy (DG), and evaluated the potential risk factors for RGC development. A retrospective database review of 438 patients who underwent DG for GC at a single institution, from 2006 to 2017, was conducted. We investigated the relationship of clinicopathological features, operative findings, and postoperative course with RGC development was estimated using Cox proportional hazard analysis. The cumulative incidences of RGC were calculated using the Kaplan-Meier method. We retrospectively analyzed 405 cases. The median patient age was 69 years, and the patient cohort consisted of 263 men and 142 women. The Billroth-I reconstruction method was used in 204 cases, Billroth-II method was used in 3 cases, and Roux-en Y method was used in 198 cases. RGC was diagnosed in 11 of the 405 patients. The median follow-up period was 5 years. The cumulative incidences of RGC calculated by the Kaplan-Meier method were 3.0%, 4.1%, and 10.5% at 5, 10, and 15 years after DG, respectively. During the initial surgery, differentiated type was significantly associated with RGC development [hazard ratio (HR): 4.71, 95% confidence interval (CI): 1.02-21.80, P=0.05]. Male sex (HR: 2.97, 95% CI: 0.64-13.75, P=0.16), old age (≥70 years) (HR: 2.72, 95% CI: 0.78-9.47, P=0.11), and synchronous multiple GC (HR: 1.31, 95% CI: 0.28-6.08, P=0.73) were not associated with RGC development. Patients who have undergone DG for differentiated type GC were statistically significantly associated with developing RGC. Intensive endoscopic surveillance would be needed for the patients who underwent DG for differentiated type GC.

Analysis of Characteristics and Risk Factors of Patients with Single Gastric Cancer and Synchronous Multiple Gastric Cancer among 14,603 Patients.

Synchronous multiple gastric cancer (SMGC) accounts for approximately 6% to 14% of gastric cancer (GC) cases. This study aimed to identify risk factors for SMGC. A total of 14,603 patients diagnosed with GC were prospectively enrolled. Data including age, sex, body mass index, smoking, alcohol consumption, family history, p53 expression, microsatellite instability, cancer classification, lymph node metastasis, and treatment were collected. Risk factors were analyzed using logistic regression analysis between a single GC and SMGC. The incidence of SMGC was 4.04%, and that of early GC (EGC) and advanced GC (AGC) was 5.43% and 3.11%, respectively. Patients with SMGC were older (65.33 years vs 61.75 years, p<0.001) and more likely to be male. Lymph node metastasis was found in 27% of patients with SMGC and 32% of patients with single GC. Multivariate analysis showed that SMGC was associated with sex (male odds ratio [OR], 1.669; 95% confidence interval [CI], 1.223 to 2.278; p=0.001), age (≥65 years OR, 1.532; 95% CI, 1.169 to 2.008; p=0.002), and EGC (OR, 1.929; 95% CI, 1.432 to 2.600; p<0.001). Survival rates were affected by Lauren classification, sex, tumor size, cancer type, distant metastasis, and venous invasion but were not related to the number of GCs. However, the survival rate of AGC with SMGC was very high. SMGC had unique characteristics such as male sex, older age, and EGC, and the survival rate of AGC, in which the intestinal type was much more frequent, was very good (Trial registration number: NCT04973631).

Haploinsufficiency by minute MutL homolog 1 promoter DNA methylation may represent unique phenotypes of microsatellite instability-gastric carcinogenesis.

Promoter DNA methylation of MutL homolog 1 (MLH1) is considered to play a causative role in microsatellite instability (MSI) carcinogenesis in primary gastric cancer, and a high MSI status is associated with treatment sensitivity to human cancers. Nevertheless, clinicopathological analysis is defective for MLH1 methylation status in a quantitative manner. We newly developed quantitative methylation specific PCR using a TaqMan probe and applied it to 138 patients with primary gastric cancer who underwent gastrectomy in addition to basic molecular features such as MSI, Epstein Barr virus, and other DNA methylation status. (1) In primary gastric cancer, median methylation value was 0.055, ranging from 0 to 124.3. First, MLH1 hypermethylation was strongly correlated with MSI-High/MSI-Low status and suppressed immunostaining (P < 0.0001). (2) The MLH1 hypermethylation was associated with advanced age (P = 0.0048), antral location (P = 0.0486), synchronous multiple gastric cancer (P = 0.0001), and differentiated histology (P = 0.028). (3) Log-rank plot analysis identified the most relevant cut-off value (0.23) to reflect gentle phenotypes in MLH1 hypermethylation cases (P = 0.0019), especially in advanced gastric cancer (P = 0.0132), which are designated as haploinsufficiency of MSI (MSI-haplo) phenotype in this study. (4) In synchronous multiple gastric cancer, MLH1 hypermethylation was not necessarily confirmed as field cancerization. (5) MSI-haplo defined by MLH1 methylation status represented distinct prognostic phenotype even after molecular classifications. MLH1 hypermethylation designated as MSI-haplo may represent unique prognostic phenotype during gastric carcinogenesis.

Value of preoperative gastroscopic carbon nanoparticles labeling in patients undergoing laparoscopic radical gastric cancer surgery

Lymph node metastasis is crucial for gastric cancer. We aim to explore the value of preoperative gastroscopic carbon nanoparticles labeling in patients undergoing laparoscopic radical gastric cancer surgery. 1199 cases undergoing laparoscopic radical gastric cancer surgery were retrospectively analyzed. 214 cases received preoperative gastroscopic carbon nanoparticles labeling. The number of total lymph nodes detected, positive lymph nodes, N staging, and operation time were analyzed. The patients received carbon nanoparticles labeling had more total lymph nodes detected (27.9±6.5 vs 22.2±4.0; P ＜ 0.001) and shorter operation time (185.9±27.8min vs 218.7±69.2min; P ＜ 0.001) compared with the control group. In addition, preoperative endoscopic carbon nanoparticles labeling improved the diagnosis rate of synchronous multiple gastric cancer (2.8% vs 0.4%; P ＜ 0.001). Preoperative endoscopic carbon nanoparticles tracer labeling is of great value in patients undergoing laparoscopic radical gastric cancer surgery. It shortens the operation time, increases the number of total lymph nodes detected for more accurate pathological TNM staging, and finds some cases of synchronous multiple gastric cancer.

Clinicopathological features and risk factors analysis of lymph node metastasis and long-term prognosis in patients with synchronous multiple gastric cancer

BackgroundAs a common malignancy, gastric cancer (GC) remains an important threat to human’s health. The incidence of synchronous multiple gastric cancer (SMGC) has increased obviously with technical advances of endoscopic and pathological examinations. Several studies have investigated the relationship between SMGC and solitary gastric cancer (SGC). However, little is known about the relationship between early and advanced SMGCs, and the independent risk factors of lymph node metastasis and prognosis in SMGC patients remain unclear.MethodsWe retrospectively collected 57 patients diagnosed as SMGC and underwent radical gastrectomies from December 2011 to September 2019. Epidemiological data and clinicopathological characteristics of all patients were recorded. Postoperative follow-up was performed by telephone or outpatient service. Chi-squared test or Fisher’s exact test was adopted in analysis of categorical data. Continuous data were analyzed by using unpaired t test. Univariate and multivariate analyses were performed to investigate the independent risk factors of lymph node metastasis and tumor recurrence of SMGC.ResultsThere were 45 males and 12 females. The average age was 62.1 years old. There were 20 patients with early SMGC and 37 patients with advanced SMGC. Most of patients (91.2%) had two malignant lesions. Tumor recurrence occurred in 8 patients, among which 7 patients died from recurrence. The rates of total gastrectomy, tumor size ≥ 2 cm, poorly differentiated type, lymph node metastasis, ulcer and nerve invasion, and preoperative CEA level were significantly higher in advanced SMGC patients compared to those with early SMGC. Lymphovascular cancer plug and preoperative CA125 were the independent risk factors of lymph node metastasis in patients with SMGC. Lymph node metastasis, nerve invasion, and preoperative AFP might be the risk factors of tumor recurrence of SMGC, but need further validation.ConclusionsIn patients with SMGC, the presence of tumor size ≥ 2 cm, poorly differentiated type, lymph node metastasis, ulcer, nerve invasion, and relatively high preoperative CEA level might indicate the advanced SMGC. More attention should be paid to lymph node metastasis in SMGC patients with lymphovascular cancer plug and high preoperative CA125. Lymph node metastasis, nerve invasion, and preoperative AFP might be associated with recurrence of SMGC, needing further validation.

Total Tumor Volume Should be Considered as an Important Prognostic Factor for Synchronous Multiple Gastric Cancer Patients with Curative Gastrectomy.

Synchronous multiple gastric cancer (SMGC) was a special type of gastric cancer with relatively low incidence. This article was designed to demonstrate that the total tumor volume (TTV) should be treated as an important prognostic factor in SMGC patients with curative gastrectomy. This study retrospective analyzed 140 SMGC patients who received curative gastrectomy between December 2004 and December 2014 in our hospital. Clinicopathological features, preoperative evaluation, surgical treatment, and outcome parameters were reviewed and analyzed. This study applied univariate and multivariate analyses to identify the most significant prognostic factors. In the univariate analysis, the TTV, pTTVNM, pN stage, pT of main tumor were all significant prognostic factors in SMGC patients (all P < 0.05). In the multivariate analysis, pN stage, TTV and pTTVNM were confirmed to be independent prognostic factors (all P < 0.05). In the comparison of survival analysis, the pTTVNM stage system (P < 0.05) was superior to the pTNM stage system (P > 0.05) in SMGC patients. In conclusion, the TTV should be considered as an independent prognostic factor in overall survival in SMGC patients who received curative gastrectomy. The pTTVNM stage should be recommended as a suitable staging system for SMGC patients.

White globe appearance is an endoscopic predictive factor for synchronous multiple gastric cancer.

BackgroundWhite globe appearance (WGA) is a small white lesion with a globular shape identified during magnifying endoscopy with narrow-band imaging. However, the association between WGA and synchronous multiple gastric cancer (SMGC) remains unclear.MethodsConsecutive patients who underwent endoscopic submucosal dissection for gastric cancer (GC) between July 2013 and April 2015 at our institution were eligible for this study. We excluded patients with a history of gastric tumor or gastrectomy. Patients who had more than 2 GCs in their postoperative pathological evaluation were classified as SMGC-positive, and patients who had at least 1 WGA-positive GC were classified as WGA-positive patients. The primary outcome was a comparison of the prevalence of WGA in patients classified as SMGC-positive and SMGC-negative. Univariate and multivariate analyses were performed using the following variables: WGA, age, sex, atrophy, and Helicobacter pylori (H. pylori) status.ResultsThere were 26 and 181 patients classified as SMGC-positive and SMGC-negative, respectively. Univariate analysis revealed that WGA-positive classification (50% vs. 23%, P=0.008) and male sex (88% vs. 66%, P=0.02) were significant factors associated with SMGC classification, while age ≥65 years (81% vs. 81%, P>0.99), severe atrophy (46% vs. 46%, P>0.99), and H. pylori positivity (69% vs. 65%, P=0.8) were not. In the multivariate analysis, only WGA-positive classification (odds ratio 2.78, 95% confidence interval 1.16-6.67; P=0.02) was a significant independent risk factor for SMGC.ConclusionsOur exploratory study showed the possibility of WGA as a predictive factor for SMGC. In cases of WGA-positive gastric cancer, careful examination might be needed to diagnose SMGC.

Simultaneous laparoscopic procedures in patients with synchronous multiple primary gastric and kidney cancer

To evaluate an effectiveness of simultaneous laparoscopic procedures in patients with synchronous multiple primary cancer (SMPC). We observed 3 patients (2 men and 1 woman) aged 61-78 years with synchronous multiple primary gastric and kidney cancer. Gastric tumors were localized in the lower third of the body (1) and the antrum (2), histological structure corresponded to adenocarcinoma G1 (1) and G2 (2). Kidney tumors were verified as light cell carcinoma and localized in the upper segment of the left kidney in 2 patient and right kidney in one patient. Mean dimension of tumor scheduled for resection was 4.65 cm, nephrectomy - 10.3 cm. Complexity of resection according to the RENAL scale was equal to 8 and 10. Three patients underwent laparoscopic Billroth-I distal gastrectomy, 2 - kidney resection and one patient - nephrectomy. Mean surgery time was 265±37 min, blood loss - 175±29 ml. There were no conversion and redo interventions within 30 days after surgery. Mean hospital-stay was 11±2 days. Minimally invasive technologies in patients with SMPC reduces blood loss, ICU- and hospital-stay. Earlier rehabilitation ensures the next stage of treatment in early postoperative period, while quality of life is better in comparison with traditional interventions.

Molecular characteristics of synchronous multiple gastric cancer.

Rationale: Multiple gastric cancer (MGC) is characterized by the presence of more than two different tumors in the stomach. However, the clonal relationship and carcinogenesis of MGC remain unclear. We investigated the clonal relationship and role of germline mutations in the carcinogenesis of MGC.Methods: We gathered 16 multiple gastric cancer patients. Thirty-three tumor samples and sixteen normal gastric tissue or blood samples were obtained from January 2016 to December 2017. We also conducted analyses for 208 gastric cancer and 49 esophagogastric junction cancer (GC-EGJ) tumors from TCGA. DNA extraction from our samples was conducted for whole-exome sequencing (WES).Results: Tumor mutation burden (TMB) was not statistically significant within database and our data in the GC-EGJ (P=0.0591) and GC groups (P=0.3113). The mutation spectrum and signatures also showed uniform distributions in GC and GC-EGJ groups within our data and TCGA database. Among sixteen patients, four were identified as monoclonal, in which 11, 10, 26 and 6 somatic mutations were shared within different tumors of P7, P8, P9 and P16, respectively. However, no common mutation between different tumors of the same patient was found among the other 12 patients. After identifying predisposing genes, we found that germline MSH2 and NCOR2 mutations were significantly dominant in 8/12 and 10/12 of genetic MGC patients. Additionally, all patients were identified with MSH2 mutations in cancer samples of those genetic MGC patients. Taking genetic MGCs as a whole, we identified that TP53 were significantly mutated in 14 of 25 tumor samples.Main conclusions: WES analyses are suggestive of monoclonal and polyclonal origin of MGC, which may promote the classification of MGC into genetic and metastatic MGC. For patients with genetic MGC, germline MSH2 X314_splice variants may contribute to carcinogenesis, thus prompting the consideration of more radical surgery and/or anti-PD-1/PD-L1 therapy.

High incidence of other primary malignancies in patients with synchronous multiple gastric cancers "a multi-center retrospective cohort study".

This study evaluated the relationship between synchronous multiple gastric cancer and other primary malignancies. During 2002–2013, 1094 consecutive surgically treated gastric cancer patients were enrolled. Preoperatively, we performed total colonoscopy and whole-body computed tomography. When malignancies in other organs were suspected, detailed organ-specific examinations were performed. Synchronous multiple gastric cancer occurred in 102 patients (9.3%)which was frequently observed in patients with preoperative other primary malignancies (p < 0.001). Preoperative other primary malignancy was an independent risk factor for synchronous multiple gastric cancer (p = 0.001; hazard ratio: 2.145, 95% confidence interval: 1.354–3.399) and an independent prognostic factor of overall survival in patients undergoing gastrectomy with curative intent (p = 0.021; hazard ratio: 1.481, 95% confidence interval: 1.060–2.070). Thus, patients with preoperative other primary malignancies have a high risk of synchronous multiple gastric cancer. Careful preoperative examination is recommended to improve survival.

Clinicopathologic characteristics and relevance of main and minor lesions of synchronous multiple early gastric cancer and gastric high grade intraepithelial neoplasia

Objective To investigate the clinicopathologic characteristics and relevance of main and minor lesions of synchronous multiple early gastric cancers (SMEGC) and gastric high grade intraepithelial neoplasia (GHGIN). Methods Thirty-two patients with SMEGC or/and GHGIN who were diagnosed and treated with endoscopic submucosal dissection in Nanjing Drum Tower Hospital from July 2012 to September 2016 were enrolled in this study. Their clinicopathologic characteristics were summed up, and the correlation between main and minor lesions on the size, location, endoscopic classification, pathologic type, invasion depth and vascular invasion were analyzed. Results Among the 32 patients, with mean age of 66.19±7.46 years, 90.62%(29/32) were male, 17 cases (53.3%) had family history of gastric cancer, 25 (78.13%) had smoking history, and 22 (68.75%) were alcohol users. There were 30 cases (93.75%) and 31 cases (96.88%) with mucosal atrophy and intestinal metaplasia, respectively. The size of main and minor lesions showed a positive correlation (r=0.4167, P=0.018). The endoscopic classification of major and minor lesions had no statistical significant consistency (P=0.314), but the pathologic type and invasion depth between major and minor lesions demonstrated a moderate significant positive correlation (P<0.05). The comparison of location between the main and minor lesions did not show correlation. However, it showed a significant correlation between major lesion which on the upper 1/3 of stomach and minor lesion on the lower 1/3 of stomach (r=0.463, P=0.003). Further more, when the main lesion was at posterior gastric wall, the minor lesions on lesser curvature were increased, which showed a positive correlation(r=0.417, P=0.009). Conclusion Old-age male with long-term smoking and alcohol history whose lesions combined with surrounding mucosa merger atrophy and intestinal metaplasia are considered as a high risk group in patients with SMEGC or/and GHGIN. Therefore, clinicians must keep high vigilant and make carefully observations on this group of patients during endoscopic examination, and consider the correlation between main and minor lesions to avoid misdiagnosis. Key words: Stomach neoplasms, multiple, synchronization; Early diagnosis; High grade intraepithelial neoplasia; Clinicopathologic characteristics

Clonality analysis of synchronous gastro-oesophageal junction carcinoma and distal gastric cancer by whole-exome sequencing.

Gastro-oesophageal junction (GEJ) carcinoma and distal gastric cancer (GC) have distinct epidemiology and clinical features and their relationship is uncertain. Synchronous multiple gastric cancers located mostly at proximal and distal sites provide rare specimens for investigating the comprehensive genomic relationships among these cancers in the context of identical genetic circumstances. Formalin-fixed, paraffin-embedded (FFPE) samples from 12 patients with synchronous GEJ carcinoma and distal GC were collected in this study. Whole-exome sequencing (WES) was performed using normal tissues as a control. Mutational profiling, clonality analysis, a detailed clinico-pathological review, determination of MSI status, EBER in situ hybridization (ISH), and programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunohistochemical staining were performed. Twenty-three of the 24 samples were microsatellite-stable (MSS). Subclonal analysis revealed that nine pairs of GEJ and distal GC tumours in neoadjuvant chemotherapy naïve patients developed independently from different origins. Two patients who received neoadjuvant chemotherapy shared clonal origins with highly similar somatic alterations. The remaining one patient who shared a rare mutation died within 6.2 months at the N3 stage. However, the enriched pathway identified from the overall mutation spectra in distal GC and GEJ carcinoma showed the close relationship of these cancers. Thus, although these cancers may have similar characteristics, histopathological and genetic profiling from single tumour specimens may still underestimate the mutational burden and somatic heterogeneity of multiple GCs. In addition, this series of cases also showed a PD-L1 expression rate of 58.3% and 66.7% in distal GC and GEJ carcinoma, respectively, with all the cases expressing PD-1. This result suggests the potential benefit of immunotherapeutic treatments. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Carcinoma in the Remnant Stomach During Long-Term Follow-up After Distal Gastrectomy for Gastric Cancer: Analysis of Cumulative Incidence and Associated Risk Factors.

The number of patients with remnant gastric cancer following resection of gastric cancer may increase. The aims of this study were to investigate the development of remnant gastric cancer after distal gastrectomy for gastric cancer and to examine its cumulative incidence, clinicopathological characteristics, and risk factors. We examined 437 patients with relapse-free survival for 5years or more after distal gastrectomy with Billroth I reconstruction for gastric cancer performed between 1985 and 2005. A total of 17 patients suffered from remnant gastric cancer. The cumulative incidence was 3.7% at 10years and 5.4% at 20years. The median time until development of remnant gastric cancer was 79months (range 30-209months). The presence of synchronous multiple gastric cancers was a significant independent risk factor for remnant gastric cancer (hazard ratio 4.036; 95% confidence interval 1.478-11.02; P=0.006). Of the 17 patients, the 13 whose remnant gastric cancer was detected via regular endoscopy showed better prognoses than the patients detected by other means (P<0.001). The cumulative incidence of remnant gastric cancer was 5.4% at 20years. In particular, patients who had multiple gastric cancers at initial gastrectomy were at higher risk for remnant gastric cancer. Therefore, long-term endoscopic surveillance is important.

The impact of pre-resection endoscopic examination time on the rate of synchronous gastric neoplasms missed during endoscopic treatment.

Synchronous multiple gastric cancers have been reported in up to 14% of patients, but few efforts have been made to optimize techniques for detection of multiple neoplasms. We sought to evaluate whether the length of endoscopic examination before endoscopic resection affected the detection rates of synchronous gastric neoplasms. Among patients referred for endoscopic treatment of gastric neoplasms (n = 1,017), we enrolled those in whom at least one other synchronous neoplasm was found during pre-resection endoscopy or during the 1-year follow-up examination. Pre-resection endoscopic examination time was compared between those in whom multiple neoplasms were completely diagnosed before resection (complete examination group) and those in whom multiple neoplasms were not fully diagnosed prior to resection but were found during follow-up evaluation (incomplete examination group). Eighty-three patients were included in the study. We found no significant difference in any of the multiplicity, location, gross appearance, size, or resection type of primary lesion between the complete (n = 46) and incomplete examination (n = 37) groups. The complete examination group had a significantly longer examination time compared to the incomplete examination group (6.5 ± 2.4min vs. 3.8 ± 1.8min, respectively; P < 0.001). The synchronous lesions most commonly presented as the flat type (42/94 lesions, 45%) and were smaller than the primary lesions (10.0 ± 7.4mm vs. 14.3 ± 9.1mm, respectively; P = 0.002). Endoscopists should consider the possibility of synchronous gastric neoplasms and examine the whole stomach, thus allowing adequate time to reduce the risk of missed lesions.

Relationship between the Degree of Endoscopic Atrophy of the Gastric Mucosa and Carcinogenic Risk

Background: The relationship between Helicobacter pylori infection and gastric cancer has been demonstrated, and the risk of gastric cancer occurrence is known to increase with the progression of atrophic changes associated with chronic gastritis. Endoscopic evaluation of the degree and extent of atrophy of the gastric mucosa is a simple and very important means of identifying a group at high risk for gastric cancer. This study aimed to clarify the carcinogenic risk in relation to the degree of atrophy. Methods: A total of 27,777 patients (272 with early gastric cancer and 135 with advanced gastric cancer) were included in this study. Endoscopically evaluated atrophy of the gastric mucosa was classified as C-0 to O-3 according to the Kimura and Takemoto classification system. Results: The cancer detection rate in relation to the degree of gastric mucosal atrophy was 0.04% (2/4,183 patients) for C-0, 0% (0/4,506) for C-1, 0.25% (9/3,660) for C-2, 0.71% (21/2,960) for C-3, 1.32% (75/5,684) for O-1, 3.70% (140/3,780) for O-2 and 5.33% (160/3,004) for O-3. As to the proportions of differentiated and undifferentiated cancers, the latter were relatively frequent in the C-0 to C-2 groups, but differentiated cancers became predominant as atrophy progressed. On the other hand, the number of both differentiated and undifferentiated cancers detected increased as gastric mucosal atrophy progressed. In addition, open-type atrophy was found in 29 (96.7%) of 30 patients with synchronous multiple gastric cancers and in all 20 patients with metachronous multiple gastric cancers. Conclusion: Endoscopic evaluation of gastric mucosal atrophy can provide a simple and reliable predictive index for both current and future carcinogenic risk.

Synchronous multiple early gastric cancer diagnosed before treatment ; report of two cases

Recently, synchronous multiple early gastric cancers are being increasingly reported due to the aging of society and development of high-performance endoscopy techniques. We present two cases of synchronous multiple early gastric cancers in which the diagnosis was made before the treatment. In Case 1, three pedunculated lesions measuring approximately 10 mm in diameter and one depressed lesion measuring 20 mm in diameter were detected endoscopically in the gastric antrum, and examination of biopsy specimens revealed the diagnosis of cancer for all the lesions. Laparoscopic subtotal gastrectomy was performed, and histology of the resected tissue revealed intramucosal well-differentiated tubular adenocarcinoma in the three pedunculated lesions and intramucosal poorly differentiated adenocarcinoma in the depressed lesion. In Case 2, two depressed lesions measuring approximately 10 mm in diameter and one pedunculated lesion measuring 3 mm in diameter detected in the gastric body were treated by endoscopic submucosal resection. All the resected lesions were diagnosed histopathologically as intramucosal well-differentiated tubular adenocarcinomas. Histopathological examination revealed evidence of atrophic gastritis with intestinal metaplasia due to H. pylori infection in the background gastric mucosa in both the cases, and the mucin expression phenotype of the gastric cancer was the gastric phenotype in the three pedunculated lesions of Case 1 and the intestinal phenotype in all the three lesions in Case 2. We suggest that the possible presence of synchronous multiple cancerous lesions, e.g., well-differentiated adenocarcinoma located in the atropic gastric mucosa, should be investigated endoscopically in patients diagnosed as having early gastric cancer.

Incidence of metachronous gastric cancer in the remnant stomach after synchronous multiple cancer surgery

In the preoperative evaluation for gastric cancer, high-resolution endoscopic technologies allow us to detect small accessory lesions. However, it is not known if the gastric remnant after partial gastrectomy for synchronous multiple gastric cancers has a greater risk for metachronous cancer. The purpose of this study was to determine the incidence of metachronous cancer in this patient subset compared with that after solitary cancer surgery. Data on a consecutive series of 1,281 patients gastrectomized for early gastric cancer from 1991 to 2007 were analyzed retrospectively. The 715 gastric remnants after distal gastrectomy were periodically surveyed by endoscopic examination in Shikoku Cancer Center. Among those surveyed cases, 642 patients were pathologically diagnosed with solitary lesion (SO group) and 73 patients with synchronous multiple lesions (MU group) at the time of the initial surgery. In the follow-up period, 15 patients in the SO group and 3 patients in the MU group were diagnosed as having metachronous cancer in the gastric remnant. The cumulative 4-year incidence rate was 1.9 % in the SO group and 5.5 % in the MU group. The difference did not reach the significant level by the log-rank test. The incidence of metachronous cancer is higher after multiple cancer surgery; however, the difference is not statistically significant.

Eleven metachronous early gastric cancers in an elderly woman.

We report on a patient with 11 metachronous multiple early gastric cancers treated by gastrectomy after endoscopic resection. An 87-year-old Japanese woman was admitted to our hospital for treatment of four synchronous multiple early gastric cancers detected by endoscopic examination. The patient had a history of two endoscopic treatments for four metachronous early gastric cancers. The pathological findings of four lesions resected by endoscopic resection and four biopsy specimens showed well-differentiated carcinoma. In March 2012, we performed a distal gastrectomy for four lesions. The surgical specimen revealed 3minute lesions after surgery in addition to these four lesions. Histologically, all seven lesions were intramucosal well-differentiated adenocarcinomas without vascular invasion. Although the incidence of synchronous and metachronous early gastric cancer is reportedly 11-14.5% and 8.5-14%, respectively, only two or three lesions are generally present. Moreover, multiple early gastric cancers usually originate as differentiated adenocarcinoma in male elderly patients with intestinal metaplasia. In the present case, there were multiple early gastric cancers, whose origin may be correlated with the background of intestinal metaplasia, in excess of the number generally expected.

Is there a Robust Predictor for the Remnant Gastric Cancer After Gastrectomy for Synchronous Multiple Gastric Cancer? Reply

To the Editor, We acknowledge the constructive comment by Hottenrott et al. to our report concerning the robust predictors of remnant gastric cancer after gastrectomy for synchronous multiple gastric cancers. He suggested that although our findings were determined by using a large number of cases, there are several weakness: (1) our study, which is based on a retrospective analysis with absolute number of incidence of remnant gastric cancer, is small and the combination of multiple lesion with undifferentiated type as an initial lesion is even more rare; (2) our study did not show a relationship between timing of development of remnant gastric cancer and tumor-free distance; (3) our study did not show the genetic background of the patients, particularly the status of CDH1, which is an important marker of remnant gastric cancer. The incidence of remnant gastric cancer is reported to be approximately 1% and the development of remnant gastric cancer after gastrectomy for synchronous multiple gastric cancer is an even rarer event; thus, it is quite challenging to establish the solid risk factors in a prospective manner [1]. Additionally, the situation could be complicated because there is multiple definitions of ‘‘remnant gastric cancer’’ in the world. We examined the relationship between the timing of the development of remnant gastric cancer and tumor-free distance at initial surgery and found that there was no significant correlation (r = 0.445, P = 0.375; two-tail) nor did it show the trend that close surgical margin is potentially associated with early development of remnant gastric cancer. Regarding the issue of molecular paradigm in the development of remnant gastric cancer, exploration of the predictor in the aspect of genetic background is fascinating. It is possible that status of CDH1 is one of the most important predictors for the development of remnant gastric cancer [2]. However, considering that treatment with endoscopic mucosal dissection (ESD) has been widely accepted both for primary gastric cancer and remnant gastric cancer [3], total gastrectomy may be excessive treatment for patients with early gastric cancer who are candidates for ESD. Thus, we believe that the status of single genetic marker is not enough for the consideration of initial total gastrectomy as the prevention purpose for remnant gastric cancer in patients with gastric cancer who are candidates for partial gastrectomy.